Graves' Disease
Conditions
Interventions
investigational material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code : 243 Thyroid and para-thyroid hormone preparations
Dosage and Administration for Investi
Sponsors
Nippon Smith Yakuhin Kabusiki Kaisha
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must satisfy all of the following criteria to be enrolled in the study: 1. Male or female subjects aged between 20 and 75 years of age inclusive, at the time of signing the informed consent form. 2. Sign an informed consent document indicating they understand the purpose of and procedure required for the study and are willing to participate in the study. 3. Subjects with Graves' disease who are either: a) treated with anti-thyroid medications (without Levothyroxine (LT4)) at a stable dose for at least 6 weeks prior to obtaining consent and who are clinically and biochemically euthyroid or hyperthyroid at screening and Day -1. (Biochemical euthyroidism is defined as normal serum fT4 with low or normal TSH). OR b) not treated with anti-thyroid medications due to intolerable side effects for at least 6 weeks prior to screening and who are clinically and biochemically hyperthyroid at screening and Day-1. Graves' disease is followed by the definition of a patient who shall be said to have Graves' disease or a patient who shall be said probably to have Graves' disease in the Guideline for the diagnosis of Graves' disease 2013 issued by Japan Thyroid Association. 4. Body mall index (weight [kg]/height [m2] between 18.5 and 35.0 kg/m2(inclusive) at screening. 5. Female subjects of child bearing potential and NB: Male subjects with pregnant partners are excluded. All female subjects (and female partners of male subjects) are regarded as being of childbearing potential unless they are either post-menopausal or permanently sterilized. Post-menopausal is defined as having had, at least, 12 months spontaneous amenorrhea with an appropriate clinical profile (age, vasomotor symptom, etc.). Female may have been permanently sterrilised by means of hysterectomy, bilateral salpingectomy, bilateral oophorectomy, confirmed tubal occlusion or tubal ligation. 6. Women of childbearing potential should only be dosed after a confirmed menstrual period and/or with a progesterone level at Day-2 (or Day-1) that demonstrates a dip from baseline indicating a menstrual bleed prior to dosing. 7. Graves' disease as defined by clinical features. If available, a diagnosis of Graves' may screening, however it is not essential.
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria will be excluded from participating in the study: 1. Subjects who are pregnant, lactating or planning to become pregnant during the study. 2. Subjects with history of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator and in consultation with the Medical Monitor if required, contraindicates their participation. 3. History of anaphylaxis following any biologic or any other allergen. 4. Subjects with current or chronic history or liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 5. Subjects with a history of malignancy of any organ system treated or untreated within the past 5 years, with exception of localized basal cell carcinoma of the skin. 6. Subjects with Graves' orbitopathy with a CAS>3/7 at screening. 7. Evidence of optic neuropathy and/or corneal breakdown at screening. 8. Subjects who have fT3 and/or fT4 over measurement range at screening. 9. Subjects with significant systemic infection during the 6 weeks before dosing. 10. Subjects with a history of recurrent or chronic infection. 11. Subjects who have had a splenectomy. 12. Subjects who have had any major surgical procedure within the 8 weeks before dosing and/or if a subject has surgery planned during the study period. 13. Subjects who have had a thromboembolic event (excluding superficial) within 12 months prior to screening. 14. Subject who have any clinically significant medical history in the opinion of the Investigator(other than those due to Graves' disease). 15. Subjects who have any clinically significant abnormal physical examination finding(other than those due to Graves' disease) determined by the Investigator. 16. Subjects who have clinically significant abnormal values for safety tests (haematology, coagulation, biochemistry, thyroid function, hormone panel, or urinalysis) at screening. Day-2(or Day-1) (other than those due to Graves' disease), determined by the Investigator. 17. Subjects who have any clinically significant allergic condition(excluding non-active hay fever) as determined by the Investigator. 18. Subjects who have had a clinically significant illness as determined by the Investigator within 4 weeks before dosing. 19. Subjects currently receiving or who have received systemic corticosteroids or other immunosuppressive agents within 3 months before dosing. 20. Live attenuated vaccines within 30 days before dosing and/or planning to have live attenuated vaccines during the study period up to the EOS visit (Day100) 21. Receipt of inactive or killed vaccinations (e.g., inactive influenza) within 5days before dosing and unwilling not to receive inactive or killed vaccinations within 5 days post dose. 22. Subjects who are still participating in a clinical trial or have received an investigational products within the following time period prior to the dosing day in the current study: 3 months, 5 half-lives, or twice the duration of the biological effect of the investigational product (whichever is longer) or planning to take any investigational drug within 6 months after the dose of IMP. 23. Subjects who have donated blood or blood products or had substantial loss of blood (more than 500mL) within 3 months before the dosing or who have the intention to donate blood or blood products during the study or within 3 months after the EOS vis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety To determine the safety and tolerability of single intramuscular (IM) or single intravenous (IV) doses of K1-70 in subjects with Graves' disease. | — |
Secondary
| Measure | Time frame |
|---|---|
| pharmacokinetics pharmacodynamics To determine the pharmacokinetics of K1-70 following single IV doses of K1-70 in subjects with Graves' disease. To evaluate the immunogenic potential of K1-70 in human subjects with Graves' disease. To assess the effect of single IV Pharmacodynamic Assessments 1. Blood samples for the qualification of TSH, fT3 and fT4 will be taken indicated in the Study Plan from screening to 100 days (11th visit) after IV injection. 2. Blood samples for the qualification of TRAb, TSAb and TSBAb will be taken indicated in the Study Plan from screening to 100 days (11th visit) after IV injection. Pharmacokinetic Assessment An assay for determination of K1-70 in human serum has been developed which is designed to detect 10ng/mL of K1-70. Where possible, the following pharmacokinetic parameters will be determined for K1-70: 1) Terminal elimination rate constant(lambda z) 2) Terminal elimination half-life(t1/2) 3) Time of the maximum observed serum concentration (tmax) 4) Maximum observed serum concentration (Cmax) 5) Area under the serum concentration time curve to the last quantified concentration (AUClast) 6) Area under the serum concentration time curve at one administration interval (AUC0-Tau) 7) Area under the serum concentration time curve from time zero to infinity (AUC0-infinity) 8) Percentage of area under the serum concentration time curve that is extrapolated (AUCextrap) exploratory To investigate the correlation between baseline thyroid stimulating hormone (TSH) receptor autoantibodies (TRAb) levels and change in pharmacodynamic markers. To investigate a potential effect of K1-70 on Graves' ophthalmopathy. | — |
Countries
Japan
Outcome results
None listed